Up to 10% of the population is affected by autoimmune diseases, many of which are associated with pathogenic autoantibodies. However, available IgG reducing therapeutics have suboptimal pharmacology and pharmacodynamic effects, induce significant patient burden, cannot be co-administered with antibody therapeutics, and have mechanism-based safety and tolerability challenges.  BHV-1310 is a bispecific extracellular degrader engineered to rapidly and efficiently lower IgG via ASGPR-mediated hepatic lysosomal degradation. BHV-1310 offers mechanistic advantages including deep and fast onset of IgG-lowering with short time to maximal effect, a brief exposure, the potential for reduced immunosuppression given selectivity against IgG3, the ability to be co-administered with biologics, and lack of effects on albumin, cholesterol or triglycerides.

After a single dose of BHV-1310, IgG lowering was dose dependent in rabbits, with maximal lowering (>90%) achieved at as early as 8 hours post dose. In both single and repeat-dose studies in cynomolgus macaques dose-dependent decreases in IgG levels resulted in up to 90% reduction of circulating IgG within 24 hours after BHV-1310 administration. No changes were observed in other immunoglobulin isotypes, IgA, IgE or IgM. No significant changes occurred in clinical pathology parameters. 

BHV-1310 demonstrated rapid, robust, safe, and selective IgG reduction in rabbits and cynomolgus macaques. BHV-1310 administration resulted in IgG lowering with faster speed of onset, shortened time to maximal effect, and to a greater depth with similar doses compared with preclinical data reported for FcRn inhibitors.  BHV-1310 represents a member of a new drug class with potentially significantly improved benefit-risk for neuroinflammatory and humoral mediated autoimmune disorders.